To evaluate the relationship between viral suppression and changes in immune function, as measured by the restoration of delayed-type hypersensitivity (DTH) and lymphoproliferative (LP) responses, observed after 48 weeks of treatment with highly active antiretroviral therapy (HAART) in ACTG 315. To evaluate the durability of the antiviral and immunologic effects of long-term treatment with HAART.

Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

34

Study Completion Date:

May 2004

Detailed Description:

Given the extensive immunologic and virologic data available from ACTG 315, follow-up studies of this advanced-disease population are indicated to primarily ascertain the impact of long-term suppression of viral replication on immunologic reconstitution or re-education and the durability of the antiviral effects of HAART.

Patients continue their current ACTG 315 regimen of zidovudine plus lamivudine plus ritonavir in an open-label fashion while undergoing 6 weeks of extensive evaluations. Treatment decisions are based on baseline viral load (mean of 2 viral load measurements taken during 6-week evaluations). Patients with HIV-1 RNA less than 100 copies/ml continue the ACTG 315 regimen. Patients with HIV-1 RNA 100-3000 copies/ml may continue the ACTG 315 regimen or initiate a new HAART regimen selected by the local investigator or primary care physician. Patients with HIV-1 RNA greater than 3000 copies/ml initiate a new HAART regimen selected by the local investigator or primary care physician. [AS PER AMENDMENT 4/10/00: Changes to regimens must be done in consultation with the study team. The team acknowledges that a viable regimen may not be available for a given patient when the plasma HIV RNA level is above 3,000 copies/ml. In this case, patients may remain on their failing regimen with evaluation every 8 weeks until a viable regimen becomes available to them.] All patients are required to maintain a HAART regimen that contains at least 3 drugs, 1 of which is a protease inhibitor. [AS PER AMENDMENT 3/5/01: All patients are required to maintain a HAART regimen that is approved by the protocol chairs.] Zidovudine (ZDV), lamivudine (3TC), stavudine (d4T), didanosine (ddI), delavirdine (DLV), ritonavir (RTV), and saquinavir soft gel capsules (SQV sgc) are provided on-study. [AS PER AMENDMENT 9/19/00: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc will be supplied by the protocol for 182 weeks.] [AS PER AMENDMENT 3/5/01: The following antiretroviral medications will be supplied by the protocol for Steps 1 and 2: ZDV, 3TC, 3TC/ZDV combination tablet, d4T, ddI, DLV, RTV, and SQV sgc.] Therapy is continued for 54 weeks. [AS PER AMENDMENT 10/6/98: The initial 54-week trial is followed by an additional 2 years of long-term evaluation. Also per this amendment, protocol therapy is initiated at Week 6.] [AS PER AMENDMENT 9/19/00: The initial 54-week trial is followed by an additional 2.5 years of long-term evaluation.] [AS PER AMENDMENT 3/5/01: Step 1 has an initial 54 weeks of treatment followed by 140 weeks of long-term follow-up. Step 2 has an additional 36 weeks of long-term follow-up. Patients who complete the final visit on Step 2 (Week 230) should return to the clinic 4 weeks after receiving the last dose of study-provided medication to complete the final evaluations.] [AS PER AMENDMENT 10/6/98: Patients may co-enroll in an immunology substudy.] [AS PER AMENDMENT 6/11/99: The immunology substudy is being piloted in 3 to 4 volunteers and may not proceed until the feasibility of the pilot project is reviewed.]

Eligibility

Ages Eligible for Study:

16 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

Protocol Chair-approved antiretroviral medications or research study treatment for an HIV complication.

Treatment, maintenance, or chemoprophylaxis with approved medications for opportunistic infections.

Use of ddI is contraindicated in patients who have serum amylase or lipase values over 1.5 times the ULN (Upper Limit of Normal), fasting triglycerides of 100 mg/dl or more, or a history of pancreatitis. Use ddI with extreme caution and only if clinically indicated in patients with known risk factors. Refer to package insert for more information.]

Concurrent Treatment:

Excluded:

Systemic cytotoxic chemotherapy.

Prior Medication:

Excluded:

Any antiretroviral medications other than the zidovudine, lamivudine, and ritonavir supplied in ACTG 315 or alternative antiretrovirals not approved by protocol chairs, 48 weeks prior to study entry.

Active substance or alcohol abuse or dependence that would interfere with adherence to study requirements.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000891